BACKGROUND AND PURPOSENuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that up-regulates a diverse array of antioxidant genes and protects cells from oxidative damage. This study is designed to determine whether D-L-sulforaphane (SFN) can protect neural crest cells (NCCs), an ethanol-sensitive cell population implicated in fetal alcohol spectrum disorders, against ethanolinduced apoptosis and whether protective effects of SFN are mediated by the induction of Nrf2-mediated antioxidant response. EXPERIMENTAL APPROACHControl, SFN-treated or Nrf2-siRNA transfected NCCs were exposed to ethanol. Nrf2 activation, the expression and activities of Nrf2 downstream antioxidant proteins, reactive oxygen species generation and apoptosis were determined in control and ethanol-exposed NCCs. KEY RESULTSExposure of NCCs to SFN alone significantly increased Nrf2 activation and the expression of Nrf2 downstream antioxidants as well as the activities of the antioxidant enzymes. Treatment of NCCs with SFN along with ethanol significantly decreased ethanol-induced oxidative stress and apoptosis. In contrast, knockdown of Nrf2 by siRNA significantly increased the sensitivity of NCCs to ethanol-induced oxidative stress and apoptosis. Suppression of Nrf2 signalling in NCCs also significantly diminished SFN-mediated antioxidant response and abolished the protective effects of SFN on ethanol-induced oxidative stress and apoptosis. CONCLUSIONS AND IMPLICATIONSThese results demonstrated that Nrf2-mediated antioxidant response plays an important role in the susceptibility of NCCs to ethanol-induced oxidative stress and apoptosis and that the protection of SFN against ethanol-induced oxidative stress and apoptosis in NCCs is mediated by the induction of Nrf2 signalling. AbbreviationsARE, antioxidant response element; D3T, 3H-1,2-dithiole-3-thione; DCHFDA, 2′,7′-dichlorodihydrofluoroscein diacetate; FASD, fetal alcohol spectrum disorder; MTS, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt; NCC, neural crest cell; NQO1, NAD(P)H:quinone oxidoreductase 1; Nrf2, nuclear factor erythroid 2-related factor; ROS, reactive oxygen species; SFN, D-L-sulforaphane; SOD, superoxide dismutase BJP British Journal of Pharmacology
Ultrasound localization microscopy is a super-resolution imaging technique that exploits the unique characteristics of contrast microbubbles to side-step the fundamental trade-off between imaging resolution and penetration depth. However, the conventional reconstruction technique is confined to low microbubble concentrations to avoid localization and tracking errors. Several research groups have introduced sparsity- and deep learning-based approaches to overcome this constraint to extract useful vascular structural information from overlapping microbubble signals, but these solutions have not been demonstrated to produce blood flow velocity maps of the microcirculation. Here, we introduce Deep-SMV, a localization free super-resolution microbubble velocimetry technique, based on a long short-term memory neural network, that provides high imaging speed and robustness to high microbubble concentrations, and directly outputs blood velocity measurements at a super-resolution. Deep-SMV is trained efficiently using microbubble flow simulation on real in vivo vascular data and demonstrates real-time velocity map reconstruction suitable for functional vascular imaging at super-resolution. The technique is successfully applied to a wide variety of imaging scenarios, include flow channel phantoms, chicken embryo chorioallantoic membranes, and mouse kidney, tumor, and brain imaging.
Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.
Objectives To establish the preferences and perceived barriers related to physical activity and diet programming of breast cancer survivors (BCS) to inform the development of Information and Communication Technology (ICT)-based lifestyle interventions. Methods This was a cross-sectional study of 197 BSC aged 18 years or older and diagnosed with ductal carcinoma in situ (DCIS) or Stage I-IV breast cancer. The BCS were recruited during routine oncology appointments at a Midwestern cancer center. A survey was conducted to query survivors’ level of interest in, preferences for, and perceived barriers to participating in an exercise and dietary intervention program, with a specific emphasis on ICT-based programming. Results Overall, 85% of BCS reported they would consider participating in exercise and diet intervention research. Approximately 45% of participants reported that they had received diet and/or exercise information as part of their cancer care. However, only 15% of the participants received such information from healthcare professionals with the appropriate expertise (e.g., Dietitian, Exercise Specialist). Over two-thirds of the participants reported frequent use of mobile devices and the internet, and 80% indicated comfort using these devices (e.g., tablet, smart phone). The top three preferred formats for an ICT-based diet and exercise intervention program were “website”, “mobile apps” and “e-mails”. Older participants (>60 years) were more likely to report a preference for e-mails while younger participants (<60 years) were more likely to report a preference for websites or mobile apps. The most common perceived barriers to participation in a lifestyle intervention included fatigue, family responsibility and work. Conclusions Most BCS in this study were interested in exercise and diet interventions and would be comfortable with an ICT-based format with a preference for delivery via websites, mobile apps or e-mails. Future ICT-based lifestyle interventions should be designed with consideration of BCS’ age, barriers, facilitators and other characteristics. Funding Sources USDA-NIFA Hatch Project 1,011,487
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